The “heart failure” is a generic designation of syndromes, which occur due to the inability of the heart of ejecting blood in an amount required by the organs, and is a disease having the five year survival rate of about 50% and extremely bad prognosis. Nowadays, diuretic agents, digitalis, catecholamine, angiotensine converting enzyme inhibitors, β blocking agents and the like are used for the treatment of heart failure. However, no treatment, except for heart transplantation, can completely suppress the advance of the pathology, or repair the body into a complete healthy body. Therefore, a novel and more useful medicament for the treatment of heart failure has been desired.
In order to find a novel medicament for the treatment of heart failure, a screening using an animal model of heart failure is of importance, and in paticular, an animal model which shows the pathology of the terminal heart failure in a short period and is available for evaluation of the effect on the vital prognosis (survival rate), is highly useful. At present, a rat model in which the coronary artery is ligated permanently (a coronary artery-ligated model) is generally used as a model of heart failure based on myocardial ischemia. However, this model requires a long time to advance to the pathology of the terminal heart failure, and generally requires a test period of a half year to one year for evaluation on the survival rate.
By ligating another artery to add a new load to a coronary artery-ligated model in which only the coronary artery has been constricted, the advancement of the pathology of heart failure may be accelerated. In fact, as a method to prepare an animal model of heart failure by constricting of two or more arteries, for example, Clin. Exper. Hypertension, 18, 691–712 (1996), Linz et al., discloses a method comprising starting stenosis of the abdominal artery 2 weeks before the coronary stenosis. However, in order to achieve the mortality rate of 68%, this method requires a period of 6 weeks after starting the coronary stenosis. Furthermore, J. Am. Coll. Cardiol., 12, 1318–1325 (1988), Nolan et al., discloses a method comprising starting stenosis of the proximal portion of the aorta 3 weeks before coronary stenosis. However, according to this method, the mortality rate after 1 week of the starting of the coronary stenosis is 13%, which shows no difference in comparison with the case that does not accompany stenosis of the aorta. Moreover, as a method to prepare an animal model of heart failure by simultaneously constricting two or more arteries, for example, Jap. Heart J., 38, 697–708 (1997), Anthonio et al., discloses a method comprising simultaneously starting coronary stenosis and the stenosis of the abdominal artery. However, this method requires a period of 6 to 8 weeks to prepare the pathology of heart failure.